The overall objective of this research program is to investigate the etiologic mechanisms of degeneration of tendinous tissues typically classified as "tendinosis." Since much literature regarding potential etiologic factors exists related to tendinosis of the rotator cuff of the shoulder (primarily the supraspinatus) and the clinical problem of rotator cuff tendinosis is a common problem affecting the young and old alike, the proposed investigations will use this tissue as a model. While a variety of etiologic factors for rotator cuff disease have been proposed, the most commonly discussed are an intrinsic alteration, where the tendon damage originates within the tendon; an extrinsic compression, where the superior structures surrounding the tendon cause tendon injury; and overuse syndromes which might represent repetitive trauma. The first Aim of the research program is to investigate the effect of each of the above three proposed etiologic factors. Clinically, it is believed that no single factor is sufficient to produce persistent tendinosis. More specifically, it is hypothesized that no long-term change in histologic parameters (e.g., inflammation, cellularity, collagen content), biomechanical parameters (e.g., stiffness, modulus, relaxation response), or biochemical parameters (e.g., glycosaminoglycan types, collagen types) will be evident between supraspinatus tendons subjected to any one of the etiologic factors and the appropriate control group, although short-term alterations are expected. The second Aim is to investigate the effect of combinations of the above three proposed etiologic factors. It is believed that, in combination, these factors are sufficient to produce persistent tendinosis. More specifically, it is hypothesized that a long-term change in histologic parameters, biomechanical parameters and biochemical parameters, as defined above, will be evident between supraspinatus tendons subjected to a combination of the etiologic factors and the appropriate control group. An in vivo rat model will be utilized in which each potential etiologic factor can be reproducibly investigated. The intrinsic alteration will be produced via injection of bacterial collagenase into the supraspinatus tendon of the animal. The extrinsic alteration will be produced by altering the anatomy of the acromial arch overlying the supraspinatus tendon using an Achilles tendon allograft wrapped and sutured around the acromion. The overuse alteration will be produced by exercising the rats on a treadmill for a controlled regimen. Animals undergoing each of the above alterations alone and in combination will be sacrificed at 4, 12, and 24 weeks after initiation of the alteration. The appropriate controls for each group will be used. Biomechanical, histologic, and biochemical measures of the harvested supraspinatus tendons will be obtained for comparison.